Antigen presenting cells (APCs) are required to present allergen and activate allergen specific T cells. Some populations of APCs express the high affinity IgE receptor (FcepsilonRI) and its expression can increase the efficiency of antigen presentation by 1000-fold. Given the critical importance of DCs in the initiation of allergic immune responses, we sought to examine FcepsilonRI expression by human DC subsets. We thus examined FcepsilonRI expression in the DC1 and DC2 populations, which are known to bias towards a Th1 and Th2 response, respectively. FcepsilonRI was expressed by both the precursor DC1 (pDC1) and pDC2 cells, as well as by mature tissue DC1 and DC2 cells. FcepsilonRI expression was significantly greater in allergic asthmatic subjects than in non-atopic controls. pDC1 and pDC2 expression of FcepsilonRI was highly correlated to serum IgE concentration. In a separate study, we further examined the relationship of DC expression of FcepsilonRI to IgE by dropping serum IgE concentration through the use of omalizumab (anti-IgE). During a clinical trial of omalizumab in allergic rhinitis subjects we serially examined FcepsilonRI expression in pDC1 and pDC2 cells. Omalizumab caused a significant drop in both pDC1 and pDC2 expression of FcepsilonRI, whereas there was no significant change in the placebo group. Omalizumab decreased FcepsilonRI expression by 52% and 83% for pDC1 and pDC2 cells, respectively. Furthermore, the decrease in FcepsilonRI expression was highly correlated with the drop in serum IgE, suggesting a direct relationship between the two variables. The results of both studies support the conclusion that serum IgE is a major factor driving FcepsilonRI expression by DCs. These data support the concept that novel therapeutic approaches directly targeted at FcepsilonRI expression would affect both the sensitization and effector phases of the allergen specific immune response.